Document Type : Original Article

Authors

1 Department of Surgery and Radiology, Faculty of Veterinary medicine, University of Tehran, Tehran, Iran

2 Department of Pediatric Surgery, Children’s Medical Center, School of Medicine, Tehran University of Medical Science, Tehran, Iran

3 Neuromusculoskeletal Research Center, Department of Physical Medicine and Rehabilitation, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

4 Department of Clinical Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran

5 Department of Medicine, International University of the Health Sciences, Winnipeg, Canada

6 Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

Abstract

The aim of this study was to introduce a new animal model of fecal incontinence (FI) by injecting abobotulinumtoxinA in the external anal sphincter (EAS) muscle of dogs which replaces models based on anal sphincter destructions that are invasive, mostly require surgical procedures, expensive, permanent, and painful to the animals. 4 healthy mongrel dogs were used in this study. First, they were received NaCl 0.09% (as control) injections in EAS muscle and effects were assessed by means of Electromyography (EMG) and clinically evaluated by sphincter pinch test and presence of leakage of feces for 2 weeks. Then, they received abobotulinumtoxinA in EAS muscle and reevaluated for 6 weeks to see short-term and medium-term effects of abobotulinumtoxinA injection. Saline had no significant changes in results obtained from EMG, however, there were significant decreases in amplitudes of action potentials after receiving abobotulinumtoxinA in comparison with no injection or saline injection in EAS muscle. Pinch tests were normal after saline injection assessment period, however, then started to be negative, ranging from two days after abobotulinumtoxinA injection to seven days after receiving abobotulinumtoxinA. Animals also had significant presentations of fecal incontinence (leakage of feces and cage contamination with feces) from the 1st week after receiving abobotulinumtoxinA until the 6th week after receiving abobotulinumtoxinA. AbobotulinumtoxinA caused paralysis in the EAS and producd FI conditions in dogs. This animal model was an appropriate substitute to the various invasive, expensive and also complicated procedures with an easy, feasible, noninvasive and non-painful single-stage abobotulinumtoxinA injection.

Keywords

  1. Paquette IM, Varma MG, Kaiser AM, et al. The American Society of Colon and Rectal Surgeons’ clinical practice guideline for the treatment of fecal incontinence. Dis Colon Rectum 2015; 58(7): 623-636.
  2. Whitehead WE, Rao SS, Lowry A, et al. Treatment of fecal incontinence: state of the science summary for the National Institute of Diabetes and Digestive and Kidney Diseases workshop. Am J Gastroenterol 2015; 110(1): 138-146.
  3. Johanson JF, Lafferty J. Epidemiology of fecal incontinence: the silent affliction. Am J Gastroenterol 1996; 91(1): 33-36.
  4. Rao SS, American College of Gastroenterology Practice Parameters Committee. Diagnosis and management of fecal incontinence. American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 2004; 99(8): 1585-1604.
  5. Saldana Ruiz N, Kaiser AM. Fecal incontinence - Challenges and solutions. World J Gastroenterol 2017; 23(1): 11-24.
  6. Meyer I, Richter HE. Impact of fecal incontinence and its treatment on quality of life in women. Women’s Heal (Lond) 2015; 11(2): 225-238.
  7. Oh HK, Lee HS, Lee JH, et al. Functional and histological evidence for the targeted therapy using biocompatible polycaprolactone beads and autologous myoblasts in a dog model of fecal incontinence. Dis Colon Rectum 2015; 58(5): 517-525.
  8. Jarrett ME, Dudding TC, Nicholls RJ, et al. Sacral nerve stimulation for fecal incontinence related to obstetric anal sphincter damage. Dis Colon Rectum 2008; 51(5): 531-537.
  9. Zubaidi AM. Artificial bowel sphincters for severe fecal incontinence: Are they a solution? Saudi Med J 2010; 31(9): 965-973.
  10. Evers J, Jones JFX, O’Connell PR. Systematic review of animal models used in research of origins and treatments of fecal incontinence. Dis Colon Rectum 2017; 60(6): 614-626.
  11. Highlights of prescribing information for DYSPORT® Available at: https://www.accessdata.fda.gov/drugsatf da_docs/label/2016/125274s107lbl.pdf. Accessed April 10, 2022.
  12. Hooijmans CR, IntHout J, Ritskes-Hoitinga M, et al. Meta-analyses of animal studies: an introduction of a valuable instrument to further improve healthcare. ILAR J 2014; 55(3): 418-426.
  13. Bracken MB. Why animal studies are often poor predictors of human reactions to exposure. J R Soc Med 2009; 102(3): 120-122.
  14. Institutional animal care and use committee guidebook.Available at: https://grants.nih.gov/grants/olaw/guidebook.pdf. Accessed April 10, 2022.
  15. Hajivassiliou CA, Carter KB, Finlay IG. Assessment of a novel implantable artificial anal sphincter. Dis Colon Rectum 1997; 40(6): 711-717.
  16. Balgobin S, Acevedo JF, Montoya TI, et al. Effect of repeat acute injury on contractile function of the external anal sphincter in an animal model. Int Urogynecol J 2013; 24(4): 637-643.
  17. Wai CY, Miller RT, Word RA. Effect of prolonged vaginal distention and sphincter transection on physiologic function of the external anal sphincter in an animal model. Obstet Gynecol 2008; 111(2 Pt 1): 332-340.
  18. Rahn DD, White AB, Miller RT, et al. Effects of pregnancy, parturition, and anal sphincter transection on function of the external anal sphincter in an animal model. Obstet Gynecol 2009; 113(4): 909-916.
  19. Kang SB, Lee HS, Lim JY, et al. Injection of porous polycaprolactone beads containing autologous myoblasts in a dog model of fecal incontinence. J Korean Surg Soc 2013; 84(4): 216-224.
  20. Yamaguchi I, Fujita F, Yamanouchi K, et al. A novel animal model of long-term sustainable anal sphincter dysfunction. J Surg Res 2013; 184(2): 813-818.
  21. Schwabegger AH, Kronberger P, Obrist P, et al. Functional sphincter ani externus reconstruction for treatment of fecal stress incontinence using free latissimus dorsi muscle transfer with coaptation to the pudendal nerve: preliminary experimental study in dogs. J Reconstr Microsurg 2007;23 (2): 79-85.
  22. Buchanan GN, Sibbons P, Osborn M, et al. Experimental model of fistula-in-ano. Dis Colon Rectum 2005; 48(2): 353-358.
  23. Benlice C, Yildiz M, Baghaki S, et al. Fistula tract curettage and the use of biological dermal plugs improve high transsphincteric fistula healing in an animal model. Int J Colorectal Dis 2016; 31(2): 291-299.
  24. Peng Chen Z, Morris JG Jr, Rodriguez RL, et al. Emerging opportunities for serotypes of botulinum neurotoxins. Toxins (Basel) 2012; 4(11): 1196–1222.
  25. Carruthers A, Carruthers J. Botulinum toxin. 4th Vancouver, Canada: Elsevier 2017; 45-48
  26. Jabbari B. History of botulinum toxin treatment in movement disorders. Tremor Other Hyperkinet Mov (N Y) 2016; 6: 394. doi: 10.7916/D81836S1.
  27. Walker TJ, Dayan SH. Comparison and overview of currently available neurotoxins. J Clin Aesthet Dermatol 2014; 7(2): 31-39.
  28. Nestor M, Ablon G, Pickett A. Key parameters for the use of abobotulinumtoxinA in aesthetics: onset and duration. Aesthetic Surg J 2017; 37(suppl_1): S20-S31.